This invention is related to 2,4-diaminoquinazolines. More particularly, this invention is related to the use of 2,4-diaminoquinazolines as antithrombotic agents.
A thrombus generally is defined as a plug or clot in a blood vessel or in one of the cavities of the heart, with said plug or clot remaining at the point of formation. When a thrombus is either free-floating in the blood stream or has been removed by the blood stream to a new location, it is referred to as an embolus. These two entities are responsible for a variety of disorders which are generally termed thromboembolic diseases. Such diseases include phlebothrombosis, thrombophlebitis, pulmonary embolism, retinal thrombosis, myocardial infarction, and cerebral infarction, among others.
The chemoprophylactic or chemotherapeutic management of thromboembolic diseases generally involves compounds which fall into one of three categories: (1) platelet aggregation inhibitors, (2) anticoagulants, and (3) fibrinolytic agents. The chemotherapeutic use of fibrinolytic agents is based upon the fact that fibrin frequently forms the primary structural support of a clot. Dissolution of the fibrin should result in lysis of the clot with restoration of blood flow. Anticoagulants and platelet aggregation inhibitors, on the other hand, generally are employed prophylatically. Anticoagulants are more effective in the treatment of venous thrombosis than arterial thrombosis because of slower blood flow on the venous side which permits coagulation factors, not platelets, to play an important role. While anticoagulants might not prevent the formation of a platelet-dominated thrombosis in the arterial circulation, they certainly can inhibit the stabilization and extension of that thrombosis. However, the successful prophylaxis of arterial thrombosis must deal with the etiologic role of the platelet. The value of platelet function inhibitors in venous thrombosis will be reflected by the extent to which platelets are involved in the formation of those thrombi. Certainly, within the circulatory system, there are regions of stasis in which fibrin formation would be virtually the sole participant in thrombosis, and other regions of high hemodynamic activity where the platelet nidus alone could block the vessel. Consequently, the search for new platelet aggregation inhibitors continues.